2. Academic Validation
  3. Unraveling the impact of crizotinib to promote megakaryopoiesis for alleviating thrombocytopenia in myelodysplastic neoplasms

Unraveling the impact of crizotinib to promote megakaryopoiesis for alleviating thrombocytopenia in myelodysplastic neoplasms

  • Leukemia. 2025 Aug 14. doi: 10.1038/s41375-025-02729-w.
Hiroki Kobayashi 1,  Yuta Komizo 2,  Nanami Watanabe 2,  Yu Miyata 2,  Yoshiya Ohnuma 2,  Yasushige Kamimura-Aoyagi 2,  Kanako Yuki 2,  Yoshihiro Hayashi 2 3,  Minoru Yoshida 4 5,  Yuka Harada 6,  Hironori Harada 2 7
Affiliations

Affiliations

  • 1 Laboratory of Oncology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. hkbys@toyaku.ac.jp.
  • 2 Laboratory of Oncology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
  • 3 Laboratory of Cancer Pathobiology and Therapeutics, Ritsumeikan University, Kusatsu, Japan.
  • 4 Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Wako, Japan.
  • 5 Drug Discovery Seeds Development Unit, RIKEN Center for Sustainable Resource Science, Wako, Japan.
  • 6 Department of Clinical Laboratory, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
  • 7 Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
PMID: 40813622 DOI: 10.1038/s41375-025-02729-w
Abstract

Current therapeutic options for myelodysplastic neoplasms (MDS)-associated thrombocytopenia are limited. Megakaryocyte maturation might be an innovative therapeutic strategy because its dysregulation profoundly contributes to MDS pathogenesis. Here, we identified crizotinib, a clinically approved anti-cancer drug for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung Cancer, as a potent inducer of megakaryocyte maturation. We demonstrated that crizotinib effectively induced polyploidization to increase the platelet-producing capacity of megakaryocytes derived from an MDS murine model and MDS patients by targeting Aurora kinases rather than its canonical targets, ALK/ROS1/c-MET. Importantly, crizotinib administration substantially ameliorated thrombocytopenia in our preclinical model. Our findings underscore the remarkable potential of crizotinib for drug repurposing and offer a novel therapeutic strategy for MDS patients with thrombocytopenia facing health-related quality of life concerns.

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